The principal objective of this research project is to determine whether cocaine-induced hypoxemia, cerebral vasoconstriction, and possible increases in oxidative metabolism may combine in the fetus to produce severe fetal brain tissue hypoxia which could induce intrauterine brain injury. In adults, cocaine has known vasoconstrictive effects on the cerebral circulation. Cocaine is known to induce fetal hypoxemia by reducing uterine blood flow; the normal compensatory fetal cerebral vasodilation may be blunted by these vasoconstrictive effects of cocaine, exacerbating tissue hypoxia. In addition, cocaine may increase cerebral oxidative metabolism, which would further compromise tissue oxygenation. In chronically prepared fetal sheep, vascular catheters will be placed in fetal arteries, veins, and superior sagittal sinus and in maternal arteries and veins. Electrodes will be placed for recording fetal electroencephalogram, electrocardiogram, and electromyograms. Cerebral blood flow will be measured with microspheres and cerebral metabolism will be studied by the Fick principle. Cocaine will be infused into mother and fetus to determine the effects on fetal arterial and sagittal sinus oxygenation, cerebral blood flow, cerebral oxidative and carbohydrate metabolism, and fetal behavior. Although cocaine is one of the most popular illicit drugs used during pregnancy, to date very little is known regarding the effects of cocaine on fetal physiology, the metabolic effects of cocaine on the fetal brain, or the effects of cocaine on fetal behavior. The proposed studies assume particular clinical relevance in light of recent observations of a high prevalance of brain structural .abnormalities and microcephaly in cocaine-exposed offspring. These studies will contribute to the understanding of cocaine-induced brain lesions and cocaine effects on fetal and newborn behavior as well as to the understanding of the physiology of the fetal cerebral circulation and the pharmacology of cocaine during pregnancy.